The studies proposed in this grant application focus on improved pre-clinical techniques of specific immunosuppression using anti-human thymocyte globulin in non-human primates. The project is designed to further determine the immunosuppressive action of rabbit anti-human thymocyte globulin (RAHTG) on peripheral blood mononuclear cell subpopulations and functions in rhesus monkey renal allotransplant recipients and to evaluate the effectiveness of RAHTG in enhancing allograft survival when administered in combination with donor lymphoid cells. Since rhesus monkeys are phylogenetically close to the human, share human thymus specific differentiation antigens and are effectively immunosuppressed by RAHTG, the rhesus monkey allograft recipient provides a suitable, well controlled, surrogate model for these pre-clinical studies. In previous studies we studied the effect of RAHTG on rhesus lymphocyte subpopulations and functions and showed striking associations between changes in specific immune parameters and allograft rejection. The present studies will utilize specific in vitro immune monitoring tests to individually modulate immune reactivity in rhesus renal allograft recipients. The individualization of immunosuppression may permit a more uniform and more effective level of immunosuppression, avoiding the extremes of under-suppression and over-suppression which occur with stereotype immunosuppressive drug regimes. Immune monitoring will also be used to study immune reactivity of recipient lymphocytes to specific donor allogeneic cells to determine mechanisms associated with allograft acceptance induced by recipient treatment with RAHTG and donor antigen. Hopefully a better understanding of these immunosuppressive systems in relevant pre-clinical models will permit more effective, rational application of specific immunosuppression in clinical transplantation.